METABOLISM OF HEXACHLOROBENZENE IN HUMANS - ASSOCIATION BETWEEN SERUMLEVELS AND URINARY METABOLITES IN A HIGHLY EXPOSED POPULATION

Serum and mine from 100 subjects of a general population highly expose d to airborne hexachlorobenzene (HCB) were analyzed to obtain new insi ghts into the metabolism of this ubiquitous compound HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 n g/ml. The major known metabolites of HCB were investigated in urine co llected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 mu g excreted in 24 hr [mea n +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenet hiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 mu g of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur deri vative assessed as PCBT appeared to be the main metabolite, with urina ry concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum >32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concen tration in serum; the association was stronger in males than in female s. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 m u g of PCBT excreted in urine collected over 24 hr in males (95% CI, 1 .82-2.44) and to an increase of 0.67 mu g of PCBT in females (CI, 0.33 -1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 mu g of PCP exc reted in urine collected over 24 hr; (CI, 0.34-0.95). These results sh ow that the formation of the cysteine conjugate is a quantitatively mo re important metabolic pathway in humans than the formation of PCP. Mo reover, the association found suggests that PCBT is a good urinary mar ker of HCB internal dose and glutathione-mediated metabolism.